Telomere Length and Male Fertility

Over the past decade, telomeres have attracted increasing attention due to the role they play in human fertility. However, conflicting results have been reported on the possible association between sperm telomere length (STL) and leukocyte telomere length (LTL) and the quality of the sperm parameters. The aim of this study was to run a comprehensive study to investigate the role of STL and LTL in male spermatogenesis and infertility. Moreover, the association between the sperm parameters and 11 candidate single nucleotide polymorphisms (SNPs), identified in the literature for their association with telomere length (TL), was investigated. We observed no associations between sperm parameters and STL nor LTL. For the individual SNPs, we observed five statistically significant associations with sperm parameters: considering a p < 0.05. Namely, ACYP2˗rs11125529 and decreased sperm motility (p = 0.03); PXK˗rs6772228 with a lower sperm count (p = 0.02); NAF1˗rs7675998 with increased probability of having abnormal acrosomes (p = 0.03) and abnormal flagellum (p = 0.04); ZNF208˗rs8105767 and reduction of sperms with normal heads (p = 0.009). This study suggests a moderate involvement of telomere length in male fertility; however, in our analyses four SNPs were weakly associated with sperm variables, suggesting the SNPs to be pleiotropic and involved in other regulatory mechanisms independent of telomere homeostasis, but involved in the spermatogenic process.     

Targeted editing of intronic-splicing silencer enhancement of SMN2 Exon 7 inclusion by CRISPR/Case 9

Spinal muscular atrophy (SMA) is an autosomal recessive hereditary neuromuscular disease. Exon 7 and 8 of survival of motor neuron 1 (SMN1) gene or only exon 7 homology deletion leads to the failure to produce a full-length SMN gene. The copy number of SMN2 gene with high homology of SMN1 affects the degree of disease and was the target gene for targeting therapy, in which splicing silencer in intron 7 was the key to suppress the inclusion of exon 7. In this study, we projected to use CRISPR/Case 9 for the targeted editing of intronic-splicing silencer (ISS) sequence to promote the inclusion of SMN2 exon 7 and increase the production of SMN2 full-length (FL) gene expression. It happens that there was a protospacer adjacent motif (PAM) at one end of the ISS sequence according to the design of sgRNA. The recombinant vector of sgRNA HSMN2 CRISPR/Case 9 was constructed and transfected into HEK293 cells. Sequencing results showed that the ISS sequence could be edited accurately and targeting in the predicted direction, in which deleting small fragments, inserting small amounts and mutation. Quantitative analysis of RT-PCR products by restriction enzyme of DdeI digestion showed that the FL of SMN2 increased by 8% (P < 0.05). In the primary cultured chondrocytes of SMA mice, in which sgRNA HSMN2 CRISPR/Case9 recombinant vector transfection could increase the SMN2 FL gene by 23% (P < 0.05) and significantly improve SMN protein levels (P < 0.05). CRISPR/Case 9 is an effective tool for gene editing and therapy of hereditary diseases, but it is rarely reported in the treatment of SMA diseases. This study shows that CRISPR/Case 9 was first used for the precision target of ISS sequence editing, which can effectively promote the production of SMN2 FL gene expressions, in which there was an important clinical reference value.     

Birth traits of Holstein calves compared with Holstein,Jersey, Montbéliarde,Normande, and Viking Red-sired crossbred calves

Holstein (HO) calves, 3-breed crossbred calves of Montbéliarde, Viking Red, and HO (MVH), and 3-breed crossbred calves of Normande, Jersey, and Viking Red (NJV) were compared for gestation length (GL), calf weight at birth (CW), calving difficulty (CD), and stillbirth (SB) in 2 research herds at the University of Minnesota. Calves were born from January 2009 to December 2019. For the St. Paul and Morris herds, HO calves (n = 1,121) were compared with MVH calves (n = 1,393) from primiparous and multiparous cows. For the single herd analysis at Morris, HO calves (n = 476), MVH calves (n = 922), and NJV calves (n = 405) were compared from primiparous and multiparous cows. Primiparous and multiparous births were analyzed separately because multiparous cows had multiple births, and CD and SB are likely different traits for primiparous and multiparous cows. Statistical analysis of GL, CW, CD, and SB included fixed effects of sex of calf, herd, breed group of calf, and year-season of calving. For the St. Paul and Morris herds, HO calves from primiparous (278 d) and multiparous (279 d) HO cows had shorter GL compared with MVH calves from primiparous (280 d) and multiparous (282 d) crossbred cows. The HO calves (39.4 and 43.2 kg, respectively) from primiparous and multiparous HO cows had lower CW compared with MVH calves (40.3 and 44.3 kg, respectively) from primiparous and multiparous crossbred cows. Calving difficulty and SB were not different for HO and MVH calves from primiparous and multiparous cows. For the single herd analysis at Morris, HO calves (278 and 279 d, respectively) from primiparous and multiparous HO cows had shorter GL compared with MVH calves (281 and 282 d, respectively) and NJV calves (282 and 282 d, respectively) from primiparous and multiparous crossbred cows. The CW of HO calves (38.6 and 42.0 kg, respectively) from primiparous and multiparous HO cows was lower compared with MVH calves (39.7 and 42.9 kg, respectively), but higher compared with NJV calves (35.1 and 38.0 kg, respectively) from primiparous and multiparous crossbred cows. Calving difficulty and SB did not differ for HO, MVH, and NJV calves from primiparous and multiparous cows. The longer GL for crossbred calves and higher CW for MVH calves did not increase CD and SB for primiparous and multiparous cows. Dairy producers may implement 3-breed rotational crossbreeding systems that include the HO, Jersey, Normande, Montbéliarde, and Viking Red breeds, and some breeds may increase GL and CW without an increase in CD and SB.     

Influence of thermal runaway in styrene–acrylonitrile bulk copolymerization revealed by computational fluid dynamics modeling

The computational fluid dynamics (CFD) and kinetic-based moment methods coupled approach is adopted to simulate the bulk copolymerization of styrene–acrylonitrile (SAN) in a stirred tank reactor. Numerical simulations are carried out to investigate the impacts of impeller speed, monomer ratio, initiator ratio, and initial reaction temperature on the copolymerization process and product properties. Particularly, the Chaos theory is selected as a criterion for evaluating the occurrence of the thermal runaway. The Flory's and Stockmayer's distributions are employed to calculate chain length distribution and copolymer composition distribution of copolymer. The simulation results highlight that the appearance of thermal runaway can be postponed by properly increasing the rotation speed, decreasing the initiator loadings, initial acrylonitrile contents and initial reactor temperature. Furthermore, significant differences exist in the product properties that predicted by the ideal and non-ideal models, which demonstrates that the temperature heterogeneity plays a crucial role in SAN copolymerization. This study could offer references for the safe operation and design of polymerization processes.     

基于图像处理的分梳山羊绒长度检测方法

为了提高分梳山羊绒长度检测的效率、降低测量过程中人为因素的影响,提出一种基于数字图像处理技术的分梳山羊绒长度检测流程和方法。对分梳山羊绒进行数字图像采集,将采集到的图像转换成灰度图像,对灰度图像进行滤波、二值化处理、边缘提取、拟合曲线,最后根据GB 18267-2013《山羊绒》计算分梳山羊绒的平均长度。结果表明:该方法可以获得分梳山羊绒的边缘曲线,根据曲线测得的分梳山羊绒平均长度与人工测量长度非常接近,为分梳山羊绒长度检测提供了有效的方法。     

煤矿井下小断层延伸长度定量化预测研究

以山西A矿开采的3号煤层采掘活动已揭露的小断层资料为基础,选取断层落差、倾角、延伸长度3个参数,通过多线性回归方法构建NW、NE 2个方向的断层延伸长度预本构模型,并进行现场应用。结果表明,构建的小断层预测模型预测的小断层延伸长度的准确率在90%以上,可以为后续揭露小断层延伸长度的确定提供可靠的参数指导。     

复杂顶板巷道锚杆锚索支护参数优化设计

针对复杂顶板巷道支护难、维修费用高等问题,根据原有支护参数的不足,采用FLAC^3D数值模拟软件,建立分析了复杂顶板巷道数值模型,采用单一变量实验方法,分别以顶板锚杆间排距、长度和帮部锚杆间排距、长度为研究对象,分析了顶板和帮部锚杆和锚索合理支护参数。研究为复杂顶板巷道锚杆锚索支护参数设计提供了理论基础。     

Exploring the biomechanics of walking and crowd “flow”

Crowd movement simulation models are generally based on aggregated speed and flow data collected more than 50 years ago. There appears to be no validated modelling capability to include the impact of recent and future changes in population demographics, resulting from an ageing population and increasing obesity rates. New analytical approaches and data gathering are required to successfully model crowd movement and safety for current and future generations. This study carried out (a) a review of the primary components of crowd movement, demographics and analytical techniques, (b) prototype experiments to investigate age-related aspects of space and potential points of contact and (c) a new predictive model for crowd flow analysis based on pedestrian biomechanics and anthropometric data. The model uses the physical space taken up by the biomechanical walking process and the spatial buffer between points of potential contact with other pedestrians to predict the speed of movement at different levels of congestion. The new analytical model was used to predict single file speeds (for people with different demographics in congested space), which compared well with published experimental data. The next steps for model development for wider “flows” and additional experiments to provide data sets for wider demographics are also proposed.     

Pregnancy by Assisted Reproductive Technology Is Associated with Shorter Telomere Length in Neonates

Telomere length (TL) influences the development of lifestyle-related diseases, and neonatal TL may influence their prevalence. Various factors have been reported to affect neonatal TL. Although the fetus is exposed to multiple conditions in utero, the main factors affecting the shortening of neonatal TL are still not known. In this study, we sought to identify factors that influence fetal TL. A total of 578 mother-newborn pairs were included for TL analysis. TL was measured in genomic DNA extracted from cord blood samples using quantitative PCR. The clinical factors examined at enrollment included the following intrauterine environmental factors: maternal age, assisted reproductive technology (ART) used, body mass index (BMI), gestational diabetes mellitus (GDM), maternal stress, smoking, alcohol consumption, preterm delivery, small-for-gestational-age, neonatal sex, and placental weight. Univariate and multivariate regression analyses were used to verify the relationship between neonatal TL and these clinical factors. The median neonatal TL to single-copy gene ratio was 1.0. Pregnancy with ART was among the 11 factors associated with shorter neonatal TL. From multiple regression analysis, we determined that neonatal TL was significantly shorter for pregnancies in the ART group than in the other groups. We conclude that pregnancy with ART is associated with shorter neonatal TL.     

Age-dependent size effect and fracture characteristics of ultra-high performance concrete

This paper presents an investigation of the age-dependent size effect and fracture characteristics of ultra-high performance concrete (UHPC). The study is based on a unique set of experimental data connecting aging tests for two curing protocols of one size and size effect tests of one age. Both aging and size effect studies are performed on notched three-point bending tests. Experimental data are augmented by state-of-the-art simulations employing a recently developed discrete early-age computational framework. The framework is constructed by coupling a hygro-thermo-chemical (HTC) model and the Lattice Discrete Particle Model (LDPM) through a set of aging functions. The HTC component allows taking into account variable curing conditions and predicts the maturity of concrete. The mechanical component, LDPM, simulates the failure behavior of concrete at the length scale of major heterogeneities. After careful calibration and validation, the mesoscale HTC-LDPM model is uniquely posed to perform predictive simulations. The ultimate flexural strengths from experiments and simulations are analyzed by the cohesive size effect curves (CSEC) method, and the classical size effect law (SEL). The fracture energies obtained by LDPM, CSEC, SEL, and cohesive crack analyses are compared, and an aging formulation for fracture properties is proposed. Based on experiments, simulations, and size-effect analyses, the age-dependence of size effect and the robustness of analytical-size effect methods are evaluated.